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PCDH11X variation is not associated with late-onset Alzheimer disease susceptibility

Abstract

A recent genome-wide association study and follow-up shows significant association with the protocadherin 11 X-linked (PCDH11X) gene. Carrasquillo et al. (2009) show statistical association with four PCDH11X polymorphisms (rs5984894, rs2573905, rs5941047, rs4568761) in five of seven cohorts. The combined analysis of 2356 cases and 2384 controls showed the strongest association with a P value of 2.2×10−7 with an allele-specific odds ratio of 1.30 (95% confidence interval, 1.18–1.43) at the rs5984894 polymorphism. We tested for association at these four single nucleotide polymorphisms in two independent datasets and then performed a joint analysis. Although we had adequate power to detect effect sizes with the reported odds ratios, we did not detect association between late-onset Alzheimer disease and the PCDH11X polymorphisms in our dataset of 889 cases and 850 controls, indicating that the PCDH11X association, if not a false positive, is not as strong or generalized as hypothesized earlier.

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